Prevention and Management of Diabetes Complications Part A (CVD, Hypertension and Dyslipidemia)

CVD is the major cause of morbidity and mortality for individuals with diabetes and the largest contributor to the direct and indirect costs of diabetes. Cardiovascular disease includes coronary disease, cerebrovascular disease, peripheral vascular disease and heart failure. The common conditions coexisting with type 2 diabetes (e.g., hypertension and dyslipidemia) are clear risk factors for CVD, and diabetes itself confers independent risk.

Risk Evaluation

There are three methods to evaluate the risk for cardiovascular disease including Framingham 10 year risk of general cardiovascular disease (2008 paper), Reynolds score for cardiovascular disease, and AHA method. See detail below.

Before using these tools to evaluate your patient’s risk of cardiovascular disease, make sure you read and understand the notice and disclaimer.

Table 1.Risk Factors for CVD (heart disease)

Conditions

Dyslipidemia

Hypertension

Diabetes Mellitus

Known CVD

Behavior

Smoking

Unhealthy Diet

Physical Inactivity

Obesity

Alcohol

Heredity

Family History of Heart Disease

Ethnicity and Race

Others

Older Age

Post-menopausal

Hypertension

Hypertension is a common comorbidity of diabetes, affecting the majority of patients, with prevalence depending on type of diabetes, age, obesity, and ethnicity. Hypertension is a major risk factor for both CVD and microvascular complications.

Screening and Diagnosis

Measurement of blood pressure in the office should be done by a trained individual and follow the guidelines established for nondiabetic individuals:

Measurement in the seated position, with feet on the floor and arm supported at heart level, after 5 min of rest;

Cuff size should be appropriated for the upper arm circumference;

Elevated values should be confirmed on a separate day.

Goals

People with diabetes and hypertension should be treated to a systolic blood pressure goal of <140 mmHg;

A diastolic blood pressure goal of <80 mmHg;

Lower systolic targets, such as <130 mmHg, may be appropriate for certain individuals, such as younger patients, if can be achieved without undue treatment burden.

Randomized clinical trials have demonstrated the benefit (reduction of CHD events, stroke, and nephropathy) of lowering blood pressure to <140 mmHg systolic and <80 mmHg diastolic in individuals with diabetes.

However, the evidence for benefits from lower systolic blood pressure target is limited.

The ACCORD trial examined whether blood pressure lowering to systolic blood pressure <120 mmHg provides greater cardiovascular protection than a systolic blood pressure level of 130-140 mmHg in patients with type 2 diabetes at high risk for CVD. The hazard ratio for the primary end point (nonfatal MI, nonfatal stroke, and CVD death) in the intensive group was 0.88. Of the prespecified secondary end points, only stroke and nonfatal stroke were statistically significantly reduced by intensive blood pressure treatment, with a hazard ratio of 0.59 and 0.63, respectively.

Note that the clear body of evidence that systolic blood pressure over 140 mmHg is harmful suggests that clinicians should promptly initiate and titrate therapy in an ongoing fashion to achieve and maintain systolic blood pressure below 140 mmHg in virtually all patients. Additionally, patients with long life expectancy or those in whom stroke risk is a concern might, as part of shared decision making, appropriately have lower systolic targets such as <130 mmHg. This would especially be the case if this can be achieved with few drugs and without side effects of therapy.

Treatment Strategies

Nonpharmacological Therapy

In nondiabetic individuals with elevated blood pressure, diet and exercise has been shown as effective as pharmacological monotherapy.

For diabetic individuals with mildly elevated blood pressure (systolic blood pressure >120 mmHg or diastolic blood pressure >80 mmHg), although there are no well-controlled studies to prove lifestyle therapy on prevention of the diabetes complication of CVD, this nonpharmacological therapy is reasonalbe approach.

Pharmacological Therapy

If the blood pressure is confirmed to be ≥140 mmHg systolic and/or ≥80 mmHg diastolic, pharmacological therapy should be initiated along with nonpharmacological therapy.

Lowering of blood pressure with regimens based on a variety of antihypertensive drugs, including ACE inhibitors, ARBs, β-blockers, diuretics, and calcium channel blockers, has been shown to be effective in reducing cardiovascular events.

Several studies suggested that ACE inhibitors may be superior to dihydropyridine calcium channel blockers in reducing cardiovascular events. But a variety of other studies have shown no specific advantage to ACE inhibitors as initial treatment of hypertension in the general hypertensive population.

In cohorts with diabetes, inhibitors of the renin-angiotensin system (RAS) may have unique advantages for initial or early therapy of hypertension. In a nonhypertension trial of high-risk individuals, including a larger subset with diabetes, an ACE inhibitor reduced CVD outcomes. In patients with congestive heart failure (CHF), including diabetic subgroups, ARBs have been shown to reduce major CVD outcomes, and in type 2 diabetic patients with significant nephropathy, ARBs were superior to calcium channel blockers for reducing heart failure.

Thus, pharmacological therapy for patients with diabetes and hypertension should be with a regimen that includes either an ACE inhibitor or an angiotensin receptor blocker (ARB). If one class is not tolerated, the other should be substituted.

Due to growing evidence suggesting that there is an association between increase in sleep-time blood pressure and incidence of CVD events, it is recommended that antihypertensive medication being given at bedtime.

Dyslipidemia/Lipid Management

Patients with type 2 diabetes have an increased prevalence of lipid abnormalities, contributing to their high risk of CVD. Multiple clinical trials demonstrated significant effects of pharmacological therapy on CVD outcomes in subjects with CHD and for primary CVD prevention.

Lipid Goals

1.For most patients with diabetes, the first priority of dyslipidemia therapy (unless severe hypertriglyceridemia with risk of pancreatitis is the immediate issue) is to lower LDL cholesterol to a target goal of <100 mg/dL (2.60 mmol/L).

2.A reduction in LDL cholesterol to a goal of <70 mg/dL is an option in very high-risk diabetic patients with overt CVD.

3.LDL cholesterol lowering of the magnitude of 30-40% from baseline is an acceptable outcome for patients who cannot reach LDL cholesterol goals due to severe baseline elevations in LDL cholesterol and/or intolerance of maximal, or any, statin doses. But also, those with baseline LDL cholesterol minimally above 100 mg/dL, to lower the level about 30-40% from baseline is probably more effective than to just lower it slightly below 100 mg/dL.

Life-style intervention, including MNT, increased physical activity, weight loss, and smoking cessation, may allow some patients to reach lipid goals. In those with clinical CVD or over age 40 years with other CVD risk factors, pharmacological treatment should be added to lifestyle therapy regardless of basline lipid levels. Statins are the drugs of choice for LDL cholesterol lowering and cardioprotection.

In patients other than those described above, statin treatment should be considered if there is an inadequate LDL cholesterol response to lifestyle modifications and improved glucose control, or if the patient has increased cardiovascualr risk (e.g., multiple cardiovascular risk factors or long duration of diabetes).

If initial attempts to prescribe a statin leads to side effects, clinicians should attempt to find a dose or alternative statin that the patient can tolerate. When maximally tolerated doses of statins fail to significantly lower LDL cholesterol (<30% reduction from the patient’s baseline), there is no strong evidence that combination therapy should be used to achieve additional LDL cholesterol lowering. Niacin, fenofibrate, ezetimibe, and bile acid sequestrants all offer additional LDL cholesterol lowering to statins alone, but without evidence that such combination therapy for LDL cholesterol lowering provides a significant increment in CVD risk reduction over stain therapy alone.

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